LDL Cholesterol Lowering With Evolocumab Before Percutaneous Coronary Intervention for Acute Myocardial Infarction
Abstract
Importance: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition is recommended as second- or third-line lipid-lowering therapy after myocardial infarction (MI), resulting in prolonged periods of inadequate low-density lipoprotein cholesterol (LDL-C) control. Whether in-catheterization laboratory decision of PCSK9 inhibition, started before mechanical reperfusion, could improve LDL-C control and clinical outcomes at 1 year is unknown. Objective: To evaluate evolocumab as first-line therapy vs standard care in patients with high-risk acute MI undergoing percutaneous coronary intervention (PCI). Design, Setting, and Participants: This international, phase 4, prospective randomized, open, blinded end-point adjudication study was conducted at 48 sites in 6 countries. Adults with high-risk ST-elevation MI (STEMI; aged >55 years) or non-ST-elevation MI (NSTEMI) with 1 or more additional high-risk characteristics were enrolled beginning September 29, 2021, through May 22, 2025, with final follow-up on May 22, 2026. Interventions: Patients were randomized 1:1 to receive evolocumab 140 mg subcutaneously every 2 weeks for 1 year (first injection before PCI) in addition to standard care (n = 1087) or standard care alone (n = 1074). Standard care included high-intensity oral lipid-lowering therapy with the optional PCSK9 inhibitor use per guideline indication in the control group. Main Outcomes and Measures: The primary outcome was LDL-C less than 55 mg/dL and at least 50% reduction in LDL-C from baseline at 12 months. The main clinical end point was all-cause death or unplanned cardiovascular hospitalization at 12 months. Results: Among 2161 randomized patients (mean age, 67 years; 1703 males [79%]; 1261 [58%] with STEMI; 900 [42%] with NSTEMI), the primary outcome was achieved in 792 of 970 patients (82%) with evolocumab vs 370 of 934 (40%) with standard care (adjusted odds ratio, 5.54 [95% CI, 4.50-6.82]; P < .001). At 6 weeks, median LDL-C was 16 mg/dL with evolocumab vs 56 mg/dL with standard care. The main clinical end point occurred in 159 of 1087 patients (14.6%) with evolocumab vs 165 of 1074 (15.4%) with standard care (adjusted odds ratio, 0.94 [95% CI, 0.73-1.19]; P = .59). Conclusions and Relevance: In patients with acute MI undergoing PCI, first-line evolocumab combined with high-intensity lipid-lowering therapy produced rapid and sustained LDL-C reduction, with more than 80% of patients reaching the guideline-recommended target at 1 year. However, no clinical benefit was detected during the first year of follow-up, arguing against clinically meaningful acute pleiotropic effects of PCSK9 inhibitors in addition to standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT04951856.
Authors 67
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Gilles Montalescot corresponding
Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Affiliation as printed
ACTION Study Group, Cardiology Department, Pasteur University Hospital, Nice, France
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Centre National de la Recherche Scientifique · Institut Pascal
Affiliation as printed
Institut Pascal, CNRS SIGMA UCA UMR 6602, University Hospital Gabriel Montpied, Cardiology Department, Clermont-Ferrand, France
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Inserm · Université de Poitiers · Centre Hospitalier Universitaire de Poitiers
Affiliation as printed
ACTION Study Group, University of Poitiers, Clinical Investigation Centre (Inserm 1402), Cardiology Department, Poitiers Hospital, Poitiers, France
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Affiliation as printed
ACTION Study Group, Département de Cardiologie, Les Hôpitaux de Chartres, Chartres, France
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Centre Hospitalier Métropole Savoie
Affiliation as printed
CH Chambéry Métropole Savoie, Chambéry, France
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Affiliation as printed
Cardiovascular Department, Azienda Ospedaliera Toscana Sudest, Arezzo, Italy
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Ospedale Misericordia - Grosseto
Affiliation as printed
Azienda Usl Toscana Sud Est, Ospedale Misericordia, Grosseto, Italy
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Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Lariboisière · Marqueurs cardiovasculaires en situation de stress
Affiliation as printed
Université Paris Cité, ACTION Study Group, MIRACL.ai Laboratory, University Hospital of Lariboisiere, AP-HP, Inserm MASCOT-UMRS 942, Paris, France
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University of Naples Federico II
Affiliation as printed
University of Naples Federico II, Naples, Italy
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Università degli Studi del Piemonte Orientale “Amedeo Avogadro” · Azienda Ospedaliero Universitaria Maggiore della Carita
Affiliation as printed
University of Eastern Piedmont, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy
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Affiliation as printed
ACTION Study Group, Hôpital cardiologique, Lille, France
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Affiliation as printed
ACTION Study Group, Centre Medico-Cardiologique d’Evecquemont, Evecquemont, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
Department of Pharmacology, Sorbonne Université, INSERM CIC-2503, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
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Université de Bordeaux · Centre Hospitalier Universitaire de Bordeaux
Affiliation as printed
Hôpital Cardiologique, Université de Bordeaux, Bordeaux, France
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Affiliation as printed
Department of Cardiology, Brest University Hospital, and Inserm UMR 1304 (GETBO), Brest, France
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Affiliation as printed
ACTION Study Group, Cardiology Department, Pasteur University Hospital, Nice, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Centre National de la Recherche Scientifique · Institut Pascal
Affiliation as printed
Institut Pascal, CNRS SIGMA UCA UMR 6602, University Hospital Gabriel Montpied, Cardiology Department, Clermont-Ferrand, France
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Affiliation as printed
ACTION Study Group, Cardiology Department, Pasteur University Hospital, Nice, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Assistance Publique – Hôpitaux de Paris · Hôpital Fernand-Widal · Université Paris 1 Panthéon-Sorbonne
Affiliation as printed
ACTION Study Group, Unité de Recherche Clinique, Hôpital Fernand Widal (AP-HP); SAMM EA 4543, Université Paris 1 Panthéon Sorbonne, Paris, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Pitié-Salpêtrière Hospital
Affiliation as printed
ACTION Study Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
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J. Wouter Jukema Aachen Department of Cardiology, Leiden University Medical Center Leiden and Netherlands Heart Institute
Leiden University Medical Center · Netherlands Heart Institute
Affiliation as printed
Department of Cardiology, Leiden University Medical Center, Leiden and Netherlands Heart Institute, Utrecht, the Netherlands
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Affiliation as printed
Department of Cardiology, Geneva University Hospital, Geneva, Switzerland
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Bellvitge University Hospital · Institut d'Investigació Biomédica de Bellvitge · Universitat de Barcelona
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Servicio de Cardiología, Hospital Universitario de Bellvitge, IDIBELL, Universidad de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain
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Leipzig Heart Institute · Leipzig University
Affiliation as printed
Department of Internal Medicine/Cardiology, Heart Center Leipzig at Leipzig University, Leipzig, Germany
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Affiliation as printed
Department of Cardiology, Jagiellonian University Medical College, Krakow, Poland
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Affiliation as printed
Cardiovascular Department, Azienda Ospedaliera Toscana Sudest, Arezzo, Italy
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Assistance Publique – Hôpitaux de Paris · Hôpital Fernand-Widal · Université Paris 1 Panthéon-Sorbonne
Affiliation as printed
ACTION Study Group, Unité de Recherche Clinique, Hôpital Fernand Widal (AP-HP); SAMM EA 4543, Université Paris 1 Panthéon Sorbonne, Paris, France
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for the AMUNDSEN Investigators of the ACTION Study Group
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